This Project will be a pre-Phase 1 clinical pilot study to make preliminary assessments ofthe pharmacokinetics, pharmacodynamics, distribution, safety, and acceptability of a trivalent monoclonal antibody (mAb) topical microbicide delivered as a vaginally-inserted film. The film dosage format may enable women to use it either precoitally, for convenience and rapid onset of protection, or daily, which may be more convenient, and due to repeated dosing, could provide superior evenness of distribution and higher sustained concentrations in the genital tract. Three application strategies will be assessed and compared: single-dose digital insertion modeling precoital use, multiple-daily-dose digital, and multiple-daily-dose application using Duet?, a cervical barrier device expected to provide an easy to use, low cost, reusable means to apply and retain microbicides, while providing a physical barrier to protect the vulnerable cervix. The two multiple daily dose formats will model non-coital continual application strategies. These will be the first clinical tests of these Mabs in film format, and precautions will be taken to assure the safety of study participants. To this end, there will be sequential escalation of the number of exposed participants and dose frequency, and we will employ the most sensitive methods available (colposcopy, measures of local immune response, vaginal flora, and systemic laboratory test monitoring) to detect microbicide toxicities. An innovative feature of this project will be the collection of genital tract secretions from trial participants for further laboratory studies to assess the potency of mAbs from the dissolved film in blocking HIV binding when combined with human cervicovaginal secretions.